HIGH EXPRESSION OF NKR-P1 IS NOT AN ABSOLUTE REQUIREMENT FOR NATURAL-KILLER ACTIVITY IN BDIX RATS

NKR-P1 has been identified as a triggering structure selectively expre ssed on rat natural killer (NK) cells and adherent lymphokine-activate d killer (A-LAK) cells. In vivo treatment with anti-NKR-P1 monoclonal antibody (mAb 3.2.3) was shown to induce complete inhibition of NK cyt otoxicity and elimination of LAK cell precursors in Lewis and Fisher r at strains. We investigated the effects of mAb 3.2.3 in a colon tumor model in BDIX rats. Inoculation of animals with mAb 3.2.3 even at very high doses induced a strong but incomplete inhibition of NK cytotoxic ity in nylon-wool-non-adherent spleen and peripheral blood cells. Gene ration of adherent A-LAK cells from their spleen precursors was also s trongly but not fully inhibited. We also investigated the effect of tr eatment with mAb 3.2.3 on the tumorigenicity of the NK-sensitive REGb cell line. When subcutaneously inoculated in syngeneic animals, REGb c ells induce tumors that first grow for 2 weeks, then spontaneously reg ress and disappear. In contrast with previous results using anti-asial oGM1, no significant difference in tumor growth was observed between r ats treated with mAb 3.2.3 and control animals, even with a long-term treatment. In vitro, mAb 3.2.3 exhibited the same incomplete efficienc y. Nylon-wool-non-adherent spleen cells treated with mAb 3.2.3 plus co mplement were completely free of 3.2.3(bright) cells, but retained a s ubstantial NK activity and generated LAK cells after culture with IL-2 . After an overnight incubation in standard medium of 3.2.3-depleted s pleen cells, 3.2.3(bright) cells were partially recovered and the NK c ytotoxic activity, as well as the generation of LAK cells, was signifi cantly enhanced. These results suggest that a strong expression of NKR -P1 is not required for BDIX mononuclear cells to exhibit NK function and generate LAK cells under IL-2 activation.